OBJECTIVE A unique subset of viruses appear when HIV-1 is transmitted by sexual exposure. These viruses are classified as "monocytotropic" because of their ability to infect monocyte cells in tissues and blood. We are testing whether this type of virus is absolutely required for sexual transmission and also, whether vaccines should be targeted specifically at this virus subtype. RESULTS Studies of recently infected patients showed that HIV-1 strains classified as "monocytotropic" were most abundant early in disease and may have been transmitted most efficiently. We have assessed modified viruses and recombinant simian/ human immunodeficiency viruses to determine their capacity for efficient mucosal transmission in macaques. SHIV carrying HIV envelope sequences from monocytotropic or dual-tropic viruses were transmitted efficiently cross rectal or vaginal mucosal surfaces. Viruses carrying T cell-tropic envelope genes were transmitted poorly across these barriers and established weak and transient infections. We are characterizing additional viruses and the earliest immune responses to mucosal infection in order to identify key mechanisms that link monocytotropism to efficient mucosal transmission. FUTURE DIRECTIONS Recombinant viruses developed in the Pauza laboratory, are being used to target expression of chemoatractant peptides. Expression of these molecules also affects virus replication in macrophages. We will begin testing these recombinant viruses in macaques to show whether they are immunizing or have increased pathogenicity. KEY WORDS AIDS, transmission, vaccine, molecular virology, mucosa FUNDING NIH/NCRR R01 RR11589 (M. Stevenson, Principal Investigator) PUBLICATIONS Pauza, C. D., D. Horejsh, and M. Wallace. 1998. Mucosal transmission of virulent and avirulent lentiviruses in macaques. AIDS Res. Human Retrovir. 14:S83-87. [J]